title: Neutral endopeptidase (CD10) is abundantly expressed in the epididymis and localized to a distinct population of epithelial cells--its relevance for CNP degradation.
abstract: Neutral endopeptidase (NEP, metallo-endopeptidase EC 3.4.24.11; enkephalinase, neprilysin, CD10, CALLA) represents a major regulator of bioactivity of natriuretic peptides. C-type natriuretic peptide (CNP) is present in high levels in epididymis and seminal plasma. However, detailed expression pattern and CNP-related function of NEP in the epididymis are unknown. Comparison of NEP protein levels in various organs revealed an extremely high expression in human and mouse epididymis. NEP was localized exclusively to apical (luminal) parts of epithelial cells. In man, strong NEP-immunoreactivity was associated with epithelia of efferent ducts and the epididymal duct including stereocilia. Segment-by-segment analysis in mouse revealed a distinct distribution along the epididymal duct. We also found the CNP receptor guanylyl cyclase B (GC-B) in epithelial cells of the epididymal duct. Two different NEP inhibitors decreased CNP degradation and increased CNP/GC-B-induced cGMP production by epididymal membranes, suggesting a functional involvement of NEP. Data indicate an important, previously neglected, role of NEP for regulation of luminal factors in the epididymis and suggest a novel role for CNP/GC-B in the epididymal epithelium, presumably in context of local water balance.
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, 35385 Giessen, Germany.
authors.forename: Arief
authors.initials: A
authors.lastname: Thong
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, 35385 Giessen, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Müller
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, 35385 Giessen, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Feuerstacke
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, 35385 Giessen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mietens
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, 35385 Giessen, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Stammler
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, 35385 Giessen, Germany. Electronic address: Ralf.Middendorff@anatomie.med.uni-giessen.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Middendorff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis; D004822:Epididymis / Q000166:cytology* / Q000201:enzymology*; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D020098:Natriuretic Peptide, C-Type; D015260:Neprilysin; D006162:Guanylate Cyclase; D006152:Cyclic GMP
keywords: ANP; C-type natriuretic peptide; CFTR; CNP; Epididymis; Epithelial cells; GC-B; Guanylyl cyclase B; NEP; Neutral endopeptidase (CD10); SMA; atrial natriuretic peptide; cGMP; cyclic guanosine monophosphate; cystic fibrosis transmembrane conductance regulator; guanylyl cyclase type B; neutral endopeptidase; smooth muscle actin